Objective: To examine the history and suitability of the Food and Drug Administration's (FDA) Risk Evaluation and Mitigation Strategy (REMS) for reducing the safety risks associated with the use of opioid medications, including the risks of abuse and overdose. This article will highlight recent attempts by the FDA to introduce a class wide REMS for new and existing Schedule II long-acting opioid drugs. A critique of these current REMS efforts and recommendations for the future will also be provided.
Design: A literature review and commentary design are utilized to highlight issues surrounding REMS efforts and to explore possible future directions. Expert opinion is offered to potentially guide future efforts in this arena.
Conclusions: The stated goal of the FDA's proposed class wide opioid REMS program is to decrease abuse, misuse, addiction and overdose deaths from opioid medications. While the REMS program may have theoretical capabilities for evaluating and addressing problematic drug use among prescribed patients, it is unlikely to reduce the bulk of prescription drug abuse that occurs with non-patients. Our recommendations provide some ideas on how the REMS program can be improved to achieve the goals set for it by Congress and the FDA.
Key words: REMS, risk management, FDA, opioids, abuse, misuse
The abuse of prescription medications, particularly opioids that are used to treat acute and chronic pain, has increased over the last decade to a level that some have described as "epidemic." (1) At the same time, chronic pain has remained a serious public health concern whose proper treatment with opioids may be hampered by prescribers' fears of inviting excessive and unwarranted regulatory scrutiny. (2) Further, the illicit market for prescription drugs, including controlled substances, (3) is growing rapidly not only in the United States but also throughout the world. (4)
Deaths attributed to the nonmedical use of prescription opioids have increased dramatically over the last decade. (5) In 2007, of the 27,500 fatal unintended drug overdoses in the U.S., 11,500 involved opioid analgesics. (6) As these deaths have increased, so has the public's demand for answers. This has led to congressional hearings, government inquiries, increased regulatory actions, and remedial legislation. (7)
In 2007, reacting to this problem, Congress passed an Amendment to the Food and Drug Act (hereinafter referred to as the FDAAA of 2007 or "the Act") that, among other things, expanded the FDA's authority to require sponsors of drugs with known or suspected risks of abuse and overdose to propose and implement a risk management plan as a condition for initial or continuing marketing approval. Specifically, the Act requires what is called a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of a new or existing drug outweigh its risks for adverse events. (8) For perhaps the first time in the history of the FDA, the statutory definition of a drug's adverse event was broadened to include abuse and overdose. In effect, the Act expanded the FDA's usual oversight responsibility for drug safety and efficacy to include outcomes that may occur from the nonmedical use of prescribed medications. (9) The Act authorized the Secretary of the Department of Health and Human Services, (10) when warranted, to require that drug sponsors propose a REMS plan as a condition for approving a new drug or for continuing the approval of an existing drug.
The Act requires that a REMS plan must be designed to evaluate and mitigate the risks of a drug's adverse events, which are described as follows:
A. An adverse event occurring in the course of the use of a drug in professional practice;
B. An adverse event occurring from an overdose of the drug, whether accidental or intentional;
C. An adverse event occurring from abuse of the drug;